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activation of human lymphocytes. In fact, as early as 2±24 h after cell injection,
the mRNA accumulation of a wide spectrum of human cytokines (IL-2, IFN-g,
IL-4, IL-10, TNF-a,TNF-b) is readily detectable in peritoneal cells, together
with increased levels of IL-2R( p55) and ICAM-1 mRNA. Soluble IL-2R and
ICAM-1 can be consistently detected in mouse sera and peritoneal lavages for
several weeks. Notably, an impressive up-regulation of lymphocyte activation
markers can be observed. In particular, CD69 is rapidly induced, whereas CD25
cells increase during the ®rst week and then decline, paralleling an ongoing rise
in the percentage of human leukocyte antigen (HLA)-DR and CD45RO cells.
At 2 wks after human cell transfer, the majority of the lymphocytes in the per-
itoneal environment express the memory isoform CD45RO. Human cell spread
can be easily monitored and documented by PCR analysis of human DNA in
mouse tissues. In fact, human HLA-DQa sequences can be detected in various
organs of xenochimeric mice as early as 2 h after reconstitution up to several
weeks after human PBL injection (Rizza et al., 1996).
In the light of the results summarized above, the reciprocal activation be-
tween human and mouse cells appears to be a dynamic scenario, in which the
human immune cell response and repertoire can be progressively shaped by the
strong reaction toward the murine major histocompatibility complex (MHC)
and partly killed by mouse reaction. This process can favor the escape of
human cells from mouse peritoneum as a result of vascular and mesothelium
injuries and cytokine-induced derangement of cellular tra½c through murine
endothelium.
HU-PBL-SCID MICE AND HIV INFECTION
Taking into account the scenario of events occurring in hu-PBL-SCID mice, we
have modi®ed the original model of HIV infection of hu-PBL-SCID mice de-
veloped by Mosier and co-workers based on the virus challenge 2 wks after
transplantation of human PBLs (Mosier et al., 1991). Human T lymphocytes
turn into CD45RO memory cells within 2±3 wks after transplantation ( Fig.
19.2) and can become mostly anergic ( Tary-Lehmann and Saxon, 1992; Tary-
Lehmann et al., 1995). In contrast, soon after reconstitution, human T cells are
highly activated, expressing the surface activation marker CD69, followed by
HLA-DR and CD25 expression ( Fig. 19.2). Thus, we infected hu-PBL-SCID
mice 2 h after hu-PBL injection with the X4 laboratory strain IIIB, as com-
pared with the classical model of HIV infection at 2 wks after reconstitution of
SCID mice. A marked CD4
T-cell depletion and a signi®cant reduction in
IgA, IgM, and sIL-2R serum levels and sICAM-1 in peritoneal washings were
observed in the xenochimeras infected with HIV-1 at 2 h, whereas the immune
functions of hu-PBL-SCID mice infected at 2 wks were almost comparable to
that of uninfected controls. Of interest, the IgM serum levels in infected animals
directly correlated with the levels of CD4 found in the peritoneal cavity ( Fig.
19.2).
